Portal de Periódicos da CAPES

miR-331-3p Regulates ERBB-2 Expression and Androgen Receptor Signaling in Prostate Cancer

2009; Elsevier BV; Volume: 284; Issue: 37 Linguagem: Inglês

10.1074/jbc.m109.030098

1083-351X

Michael R. Epis, Keith M. Giles, Andrew Barker, Tulene S. Kendrick, Peter J. Leedman,

Cancer-related molecular mechanisms research

MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression and are aberrantly expressed in human cancer. The ERBB-2 tyrosine kinase receptor is frequently overexpressed in prostate cancer and is associated with disease progression and poor survival. We have identified two specific miR-331-3p target sites within the ERBB-2 mRNA 3'-untranslated region and show that miR-331-3p expression is decreased in prostate cancer tissue relative to normal adjacent prostate tissue. Transfection of multiple prostate cancer cell lines with miR-331-3p reduced ERBB-2 mRNA and protein expression and blocked downstream phosphatidylinositol 3-kinase/AKT signaling. Furthermore, miR-331-3p transfection blocked the androgen receptor signaling pathway in prostate cancer cells, reducing activity of an androgen-stimulated prostate-specific antigen promoter and blocking prostate-specific antigen expression. Our findings provide insight into the regulation of ERBB-2 expression in cancer and suggest that miR-331-3p has the capacity to regulate signaling pathways critical to the development and progression of prostate cancer cells.